Nanoparticles, i.e. particles having dimensions in the general range of around 1 nm to 100 nm, have a myriad of actual and potential uses in many different fields of science and technology, ranging from electronic and structural materials engineering to medical technology. A particular feature of such particles is the high ratio of surface area to volume (an inherent feature of particle size), which can be exploited in applications where surface activity is important, although this also causes problems when handling and maintaining such particles in suspension. Stable suspensions of certain types of nanoparticles have however been known for many years, one of the earliest such examples being suspensions of gold nanoparticles. Such particles can be used in applications such as medical imaging, where a fine dispersion of a high atomic weight material can be used as an effective contrast agent, for example in X-ray imaging applications.
Superparamagnetic iron oxide (SPIO) is an example of a material available in nanoparticulate form, typically comprising nanocrystalline particles with dimensions ranging from 2 nm to 100 nm in diameter. This material has been utilised in recent years for various applications including in magnetic inks, biosensors, catalysis, magnetic-activated cell sorting and in targeted drug delivery.
The paramagnetic properties of SPIO nanoparticles are also being used and developed as contrast agents for magnetic resonance imaging (MRI). SPIO nanoparticles have a particular advantage as MRI contrast agents due to their low toxicity, particularly in comparison with existing contrast agents based on gadolinium, since iron becomes incorporated into the body to make haemoglobin upon degradation. Gadolinium-based contrast agents have a disadvantage of potential severe side effects including nephrogenic fibrosing dermopathy and other conditions. This has led to products finding their way to the market based on SPIO nanoparticles in preference to gadolinium-based agents for bowel, liver and spleen imaging. Other applications are also expected to be developed and used in the near future.
SPIO, as with most other metal oxides, is inherently insoluble in water and other solvents. The surfaces of particles of such materials can however, be treated to allow a stable colloidal suspension to be formed. Treating the surfaces of nanoparticles is commonly known as functionalising or capping. Suitably functionalised nanoparticles become effectively soluble (although the core metal oxide particle will remain undissolved), which allows for use of the particles in biomedical applications where compatibility with aqueous solvents is essential. Creating such suspensions is therefore also known as solubilising, and the suspensions are also referred to as solutions.
Current known methods for solubilising SPIO nanoparticles can involve adding a polysaccharide such as dextran as a coating agent in situ, with the coating agent being added in solution to a suspension of nanoparticles. Coating, or capping, of the particles may occur during their formation, although hydrophobic groups have also been used. Capped particles can be further functionalised for various applications such as drug delivery, diagnosis and therapy. A self-assembled monolayer (SAM), can also be formed via the addition of a functionalising group such as sulfonic or phosphonic acids, or the ferrofluid (a term for a colloid of magnetic particles in a liquid solvent) can be taken up into a liposome to form a magneto-liposome.
Elevated temperatures of up to around 260° C. are currently used to form capped SPIO nanoparticles. This can be problematic as the temperatures required limits the capping groups that can be used to those that are stable at high temperatures, thus eliminating many potential bioactive compounds. Furthermore, other methods may also lead to the requirement of additional functionalising steps and/or ligand exchange in order to solubilise the particles. This can be complex and time-consuming due to the use of additional processing steps. The required linking compounds may also lead to an increase in toxicity and thus limitations in applications, particularly in biomedical applications.
A further problem with forming coatings on nanoparticles during either formation or in subsequent solution processing is that the resulting nanoparticle suspension can have a limited shelf life, and may settle out of suspension over an extended period of time.
Iron is an important micronutrient, found in nearly all forms of life on the planet, ranging from evolutionally primitive archaea to more complex organisms such as plants and humans. It has been estimated that 30% of the world wide population is deficient in this element. Iron deficiency in humans arises when the physiological requirements cannot be met by Fe absorption from the diet and results in the reduction of both circulating haemoglobin and essential iron-containing enzymes such as catalase. The main consequences of these are: reduced psychomotor and mental development in infants, decreased immune function, poor work performance and tiredness. The most common strategy for decreasing micro-nutrient malnutrition is supplementation with pharmaceutical preparations, however this method is expensive and its viability as a long term strategy is heavily dependent on continued funding, infrastructure and a good distribution network, which cannot be guaranteed in poorer countries where iron deficiency is most prevalent.
The current method for improving iron concentration in plants is based on the addition of iron-containing fertilisers to the soil. However, this approach is very limited due to solubility issues of iron oxide, resulting in little impact on increasing iron levels in healthy plants. Recent research into fortifying iron in plants has been largely focussed on genetic engineering or other ways of improving the bioavailability of iron in the plant. Though studies into the genetic engineering of plants have shown some results, the large legislative issues and ethical concerns surrounding the implementation of genetically modified crops on a commercial scale means there is a need for alternative routes to fortification of food crops with iron.
It is an object of the invention to address one or more of the above mentioned problems.